AggreBots: configuring CiliaBots through guided, modular tissue aggregation.

Ciliated biobots, or CiliaBots, are a class of engineered multicellular tissues that are capable of self-actuated motility propelled by the motile cilia located on their exterior surface. Correlations have been observed between CiliaBot motility patterns and their morphology and cilia distribution. However, precise control of these structural parameters to generate desired motility patterns predictably remains lacking.

Molecular organization of the distal tip of vertebrate motile cilia.

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. Unlike basal bodies or axonemes, the distal tips of MCC cilia remain poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, revealing two distinct domains occupied by distinct protein constituents.

Integrative cytogenetic and molecular studies unmask "chromosomal mimicry" in hematologic malignancies.

The detection of structural variants (SVs) represents a critical component in the diagnostic evaluation and treatment of many hematologic malignancies. Although clinical SV testing mainly consists of traditional cytogenetic methodologies, technological innovations have led to alternative approaches with improved resolution. In this study, we sought to characterize the clinical impact of targeted RNA sequencing on the diagnosis of myeloid and immature lymphoid malignancies.

Inflammation-induced loss of CFTR-expressing airway ionocytes in non-eosinophilic asthma.

Background And Objective: Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies.

A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks.

A correctable immune niche for epithelial stem cell reprogramming and post-viral lung diseases.

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection.

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing.

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive.

Predicting peak inundation depths with a physics informed machine learning model.

Timely, accurate, and reliable information is essential for decision-makers, emergency managers, and infrastructure operators during flood events. This study demonstrates that a proposed machine learning model, MaxFloodCast, trained on physics-based hydrodynamic simulations in Harris County, offers efficient and interpretable flood inundation depth predictions. Achieving an average of 0.

Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.

Ultrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step U-ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue.

Loss of an extensive ciliary connectome induces proteostasis and cell fate switching in a severe motile ciliopathy.

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in and cause severe disease not explained by loss of motility.

Use of Inhaled Epoprostenol in Patients With COVID-19 Receiving Humidified, High-Flow Nasal Oxygen Is Associated With Progressive Respiratory Failure.

Background: The clinical benefit of using inhaled epoprostenol (iEpo) through a humidified high-flow nasal cannula (HHFNC) remains unknown for patients with COVID-19.

Research Question: Can iEpo prevent respiratory deterioration for patients with positive SARS-CoV-2 findings receiving HHFNC?

Study Design And Methods: This multicenter retrospective cohort analysis included patients aged 18 years or older with COVID-19 pneumonia who required HHFNC treatment. Patients who received iEpo were propensity score matched to patients who did not receive iEpo.

mTOR signaling regulates aberrant epithelial cell proliferative and migratory behaviors characteristic of airway mucous metaplasia in asthma.

Unlabelled: In asthma, the airway epithelium is hyperplastic, hypertrophied, and lined with numerous large MUC5AC-containing goblet cells (GC). Furthermore, the normal epithelial architecture is disorganized with numerous, what we here describe as, ectopic goblet cells (eGC) deep within the thickened epithelial layer disconnected from the lumenal surface. mTOR is a highly conserved pathway that regulates cell size and proliferation.

Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.

Ultrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step U-ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue.

Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress.

The forkhead transcription factor Foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation.

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation.

A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks.

Genetic transformation of the frog-killing chytrid fungus .

(), a causative agent of chytridiomycosis, is decimating amphibian populations around the world. belongs to the chytrid lineage, a group of early-diverging fungi that are widely used to study fungal evolution. Like all chytrids, develops from a motile form into a sessile, growth form, a transition that involves drastic changes in its cytoskeletal architecture.